A total of over one hundred and fifty pharmacologically active alkaloids have been characterized in skin extracts of some fifty species of dendrobatid frogs. The batrachotoxins are steroid alkaloids which by interaction with a specific site prevent inactivation of voltage-dependent sodium channels in nerve and muscle. A radioactive batrachotoxin analog is a useful ligand for this site. Binding is antagonized competitively by local anesthetics. The histrionicotoxins are spiropiperidine alkaloids. the pumiliotoxin-C class are decahydroquinolines. The gephyrotoxins are indolizidines and perhydrobenzoindolizidines. These rather non-toxic alkaloids interact with site(s) on chemosensitive (acetylcholine, glutamate) ionic channels, thereby enhancing conversion to a non-conducting state. The pumiliotoxin-A class are 6-alkylidene-indolizidines which facilitate and then block calcium-dependent excitation-secretion and excitation-contraction. Prolongation of muscle twitches appears to be related to a specific inhibition of calcium-dependent ATPase of sarcoplasmic reticulum Pumiliotoxin-B has no effect on other ATPases including the calmodulin-dependent calcium-ATPase of erythrocyte. Simpler analogs are, however, general inhibitors.